Phenotype and genotype in 52 patients with Rubinstein-Taybi syndrome caused by EP300 mutations

Patricia Fergelot; Martine Van Belzen; Julien Van Gils; Alexandra Afenjar; Christine M Armour; Benoit Arveiler; Lex Beets; Lydie Burglen; Tiffany Busa; Marie Collet; Julie Deforges; Bert B A de Vries; Elena Dominguez Garrido; Nathalie Dorison; Juliette Dupont; Christine Francannet; Sixto Garciá-Minaúr; Elisabeth Gabau Vila; Samuel Gebre-Medhin; Blanca Gener Querol; David Geneviève; Marion Gérard; Cristina Giovanna Gervasini; Alice Goldenberg; Dragana Josifova; Katherine Lachlan; Saskia Maas; Bruno Maranda; Jukka S Moilanen; Ann Nordgren; Philippe Parent; Julia Rankin; Willie Reardon; Marlène Rio; Joëlle Roume; Adam Shaw; Robert Smigiel; Amaia Sojo; Benjamin Solomon; Agnieszka Stembalska; Constance Stumpel; Francisco Suarez; Paulien Terhal; Simon Thomas; Renaud Touraine; Alain Verloes; Catherine Vincent-Delorme; Josephine Wincent; Dorien J M Peters; Oliver Bartsch; Lidia Larizza; Didier Lacombe; Raoul C Hennekam; Faculty of Medicine

doi:10.1002/ajmg.a.37940

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Phenotype and genotype in 52 patients with Rubinstein-Taybi syndrome caused by EP300 mutations

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Phenotype and genotype in 52 patients with Rubinstein-Taybi syndrome caused by EP300 mutations

Patricia Fergelot, Martine Van Belzen, Julien Van Gils, Alexandra Afenjar, Christine M Armour, Benoit Arveiler, Lex Beets, Lydie Burglen, Tiffany Busa, Marie Collet, …

American journal of medical genetics. Part A, Vol.170(12), pp.3069-3082

12/2016

DOI: https://doi.org/10.1002/ajmg.a.37940

PMID: 27648933

Résumé

Adult

Chromatin Assembly and Disassembly - genetics

CREB-Binding Protein - genetics

E1A-Associated p300 Protein - genetics

Female

Genetic Association Studies

Genetic Predisposition to Disease

Genotype

Humans

Male

Middle Aged

Mutation, Missense - genetics

Pre-Eclampsia - genetics

Pre-Eclampsia - physiopathology

Pregnancy

Rubinstein-Taybi Syndrome - genetics

Rubinstein-Taybi Syndrome - pathology

Sequence Deletion

Rubinstein-Taybi syndrome (RSTS) is a developmental disorder characterized by a typical face and distal limbs abnormalities, intellectual disability, and a vast number of other features. Two genes are known to cause RSTS, CREBBP in 60% and EP300 in 8-10% of clinically diagnosed cases. Both paralogs act in chromatin remodeling and encode for transcriptional co-activators interacting with >400 proteins. Up to now 26 individuals with an EP300 mutation have been published. Here, we describe the phenotype and genotype of 42 unpublished RSTS patients carrying EP300 mutations and intragenic deletions and offer an update on another 10 patients. We compare the data to 308 individuals with CREBBP mutations. We demonstrate that EP300 mutations cause a phenotype that typically resembles the classical RSTS phenotype due to CREBBP mutations to a great extent, although most facial signs are less marked with the exception of a low-hanging columella. The limb anomalies are more similar to those in CREBBP mutated individuals except for angulation of thumbs and halluces which is very uncommon in EP300 mutated individuals. The intellectual disability is variable but typically less marked whereas the microcephaly is more common. All types of mutations occur but truncating mutations and small rearrangements are most common (86%). Missense mutations in the HAT domain are associated with a classical RSTS phenotype but otherwise no genotype-phenotype correlation is detected. Pre-eclampsia occurs in 12/52 mothers of EP300 mutated individuals versus in 2/59 mothers of CREBBP mutated individuals, making pregnancy with an EP300 mutated fetus the strongest known predictor for pre-eclampsia. © 2016 Wiley Periodicals, Inc.

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Titre: Phenotype and genotype in 52 patients with Rubinstein-Taybi syndrome caused by EP300 mutations
Créateurs - sans rôle: Patricia Fergelot - Department of Genetics, and INSERM U1211, University Hospital of Bordeaux, Bordeaux, France
Martine Van Belzen - Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
Julien Van Gils - Department of Genetics, University Hospital Center, Bordeaux, France
Alexandra Afenjar - Assistance Publique – Hôpitaux de Paris
Christine M Armour - Regional Genetics Unit, Children's Hospital of Eastern Ontario, Ottawa, Canada
Benoit Arveiler - Department of Genetics, and INSERM U1211, University Hospital of Bordeaux, Bordeaux, France
Lex Beets - Department of Pediatrics, Academic Medical Center, Amsterdam, The Netherlands
Lydie Burglen - Assistance Publique – Hôpitaux de Paris
Tiffany Busa - Assistance Publique Hôpitaux de Marseille
Marie Collet - Département de Génétique, Hospital Necker-Enfants Malades, AP-HP, Paris, France
Julie Deforges - Department of Genetics, University Hospital Center, Bordeaux, France
Bert B A de Vries - Radboud University Medical Center
Elena Dominguez Garrido - Center for Biomedical Research, Logrono-La Rioja, Spain
Nathalie Dorison - Departement de Neuropédiatrie, Institut Jérôme Lejeune, Paris, France
Juliette Dupont - Serviço de Genética, Departamento de Pediatria, Hospital de Santa Maria, CHLN, Lisboa, Portugal
Christine Francannet - Service de Génétique Médicale, CHU Estaing, Clermont-Ferrand, France
Sixto Garciá-Minaúr - Institute of Medical and Molecular Genetics, University Hospital La Paz, Madrid, Spain
Elisabeth Gabau Vila - Genetics Clinic, Hospital de Sabadell, Corporació Sanitària Parc Taulí, Sabadell, Spain
Samuel Gebre-Medhin - Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden
Blanca Gener Querol - Hospital de Cruces, Baracaldo, Spain
David Geneviève - Service de Génétique Médicale, Hospital Arnaud de Villeneuve, CHU Montpellier, Montpellier, France
Marion Gérard - Service de Génétique, Hospital Clémenceau, CHU de Caen, Caen, France
Cristina Giovanna Gervasini - University of Milan
Alice Goldenberg - Unité de Génétique Clinique, Hospital Charles Nicolle, CHU Rouen, Rouen, France
Dragana Josifova - Department of Medical Genetics, Guy's and St Thomas Hospital, London, United Kingdom
Katherine Lachlan - Princess Anne Hospital
Saskia Maas - Amsterdam UMC Location University of Amsterdam
Bruno Maranda - Laboratoire de Médecine Génétique, CHUQ Pavillon CHUL, Saint Foy, Canada
Jukka S Moilanen - PEDEGO Research Unit, and Medical Research Center Oulu, Department of Clinical Genetics, University of Oulu, Oulu University Hospital, Oulu, Finland
Ann Nordgren - Karolinska University Hospital
Philippe Parent - Département de Pédiatrie et Génétique Médicale, Hospital Augustin Morvan, CHU Brest, Brest, France
Julia Rankin - Royal Devon University Healthcare NHS Foundation Trust
Willie Reardon - Our Lady's Hospital for Sick Children, Crumlin, Ireland
Marlène Rio - Assistance Publique Hôpitaux de Marseille
Joëlle Roume - Unité de Génétique Médicale, CHI Poissy, Saint Germain en Laye, France
Adam Shaw - Department of Medical Genetics, Guy's and St Thomas Hospital, London, United Kingdom
Robert Smigiel - Department of Paediatrics, Wroclaw Medical University, Wroclaw, Poland
Amaia Sojo - Hospital de Cruces, Baracaldo, Spain
Benjamin Solomon - Division of Medical Genomics, Inova Translational Medical Institute, Falls Church
Agnieszka Stembalska - Department of Genetics, Wroclaw Medical University, Wroclaw, Poland
Constance Stumpel - Department of Clinical Genetics and School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands
Francisco Suarez - Service de Génétique, Hospital Virgen de la Salud, Toledo, Spain
Paulien Terhal - Department of Medical Genetics, University Medical Centre Utrecht, Utrecht, The Netherlands
Simon Thomas - Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, United Kingdom
Renaud Touraine - Hôpital Nord
Alain Verloes - Hôpital Robert-Debré
Catherine Vincent-Delorme - Centre Hospitalier Universitaire de Lille
Josephine Wincent - Department of Molecular Medicine and Surgery, and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden
Dorien J M Peters - Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
Oliver Bartsch - Institute of Human Genetics, University Medical Centre, Mainz, Germany
Lidia Larizza - Department of Health Sciences, University of Milan, Milan, Italy
Didier Lacombe - Department of Genetics, and INSERM U1211, University Hospital of Bordeaux, Bordeaux, France
Raoul C Hennekam - Amsterdam UMC Location University of Amsterdam
Faculty of Medicine
Détails de publication: American journal of medical genetics. Part A, Vol.170(12), pp.3069-3082
Identifiants: 99141115809311
Unité académique: Cell souches plasticité cellul régénérat tissulaire immuno des maladies inflamm - IRMB
Langue: English
Type de ressource: Journal article